Editors' ChoiceCancer Imaging

The Hunt for Red October

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Science Translational Medicine  23 Mar 2011:
Vol. 3, Issue 75, pp. 75ec41
DOI: 10.1126/scitranslmed.3002407

For many types of tumors, growing larger than 1 to 2 mm requires angiogenesis, or proliferation of new blood vessels. To accomplish this, tumors turn on an angiogenic switch. Detecting expression of angiogenic markers in vivo would allow early screening for cancers and killing of tumors that are still at a curable stage. In addition, this ability would potentially give us a method to spy on and monitor treatment with antiangiogenic chemotherapeutic agents.

Ultrasound (medical sonar) microbubble (MB) contrast agents are made of perfluorocarbons and have diameters of up to several micrometers, causing them to stay within the blood vessels when injected intravenously. The captains of the featured research, Despande et al., labeled these MBs to target three well-characterized molecular markers of tumor angiogenesis—αvβ­3 integrin, vascular endothelial growth factor receptor 2 (VEGFR2), and endoglin. They then injected these labeled MBs into mice, which were xenografted with breast, ovarian, or pancreatic cancer, and imaged these cancers using high-frequency ultrasound. Because these MBs remain within the vascular compartment, the authors hypothesized that targeted MBs would allow visualization of molecular markers of angiogenesis expressed on tumor vascular endothelial cells. They found that targeted MBs bound at significantly higher levels to cells that were later shown to express angiogenic markers than did control MBs without any attached targeting molecules.

This is an important first step in using MBs to target various molecular markers expressed on vascular endothelial cells. However, obstacles to clinical adoption remain. First, it is not clear whether xenografted tumors behave the same as de novo tumors in terms of angiogenesis: The xenografting process could stimulate angiogenesis and increase expression of these markers. Second, MB contrast agents are controversial. Although other nations have readily approved their use, the U.S. Food and Drug Administration has issued a black box warning after several deaths were reported, which has been a stumbling block to widespread use. Yet, the cold war against cancer may someday be won if the difficult task of hunting for elusive cancer cells in a vast ocean of blood is approached with medical sonar coupled with cunning and persistence.

N. Deshpande et al., Tumor angiogenic marker expression levels during tumor growth: Longitudinal assessment with molecularly targeted microbubbles and US imaging. Radiology 259, 804–811 (2011). [Abstract]

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